Clinical manufacture of therapeutic proteins is an expensive, large scale endeavor. Demand for greater quantities of therapeutic recombinant proteins has driven advances in cell culture processing which have resulted in dramatically increased product titer. High titer cell culture processes are typically produced by maintaining high viable cell densities over longer culture durations. A corresponding increase in the biomass solids (viable and non-viable cells) and the submicron cellular debris particles are also observed. The higher burden of solids and submicron cellular debris particles can challenge mammalian cell culture harvest processes, making the harvest process less effective at removing the debris without a substantial loss of product capacity.
Cationic polymer flocculents are used for many applications ranging from potable water purification, waste water treatment, uses in the petroleum, mining and paper making industries, cosmetics and medical uses, and have also been used to encapsulate mammalian cells and enzymes and to flocculate microbial cell cultures. However, for use in a commercial scale mammalian cell harvest process, lengthy flocculation settling time can be problematic, resulting in a harvest process that is time consuming and less efficient than standard harvest practices.
There is a continuing need to improve mammalian cell culture harvest methods, particularly commercial scale methods. Any improvements that allow for quicker recovery times and/or greater recovery can lead to reduced costs associated with manufacturing protein therapeutics. The invention fulfills this need by providing a quick and efficient method of cell culture harvest.